Neuronal PAS Domain 2 (Npas2)-Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction.
Npas2
circadian rhythm
collagen
fibroblast
wound healing
Journal
Anatomical record (Hoboken, N.J. : 2007)
ISSN: 1932-8494
Titre abrégé: Anat Rec (Hoboken)
Pays: United States
ID NLM: 101292775
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
12
09
2018
revised:
11
12
2018
accepted:
17
12
2018
pubmed:
10
3
2019
medline:
17
2
2021
entrez:
10
3
2019
Statut:
ppublish
Résumé
The circadian clock, which consists of endogenous self-sustained and cell-autonomous oscillations in mammalian cells, is known to regulate a wide range of peripheral tissues. The unique upregulation of a clock gene, neuronal PAS domain protein 2 (Npas2), observed along with fibroblast aging prompted us to investigate the role of Npas2 in the homeostasis of dermal structure using in vivo and in vitro wound healing models. Time-course healing of a full-thickness skin punched wound exhibited significantly faster wound closure in Npas2-/- mice than wild-type (WT) C57Bl/6J mice. Dorsal skin fibroblasts isolated from WT, Npas2+/-, and Npas2-/- mice exhibited consistent profiles of core clock gene expression except for Npas2 and Per2. In vitro behavioral characterizations of dermal fibroblasts revealed that Npas2-/- mutation was associated with increased proliferation, migration, and cell contraction measured by floating collagen gel contraction and single-cell force contraction assays. Npas2 knockout fibroblasts carrying sustained the high expression level of type XII and XIV FAICT collagens and synthesized dermis-like thick collagen fibers in vitro. Confocal laser scanning microscopy demonstrated the reconstruction of dermis-like collagen architecture in the wound healing area of Npas2-/- mice. This study indicates that the induced Npas2 expression in fibroblasts may interfere with skin homeostasis, wound healing, and dermal tissue reconstruction, providing a basis for novel therapeutic target and strategy. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
Identifiants
pubmed: 30851151
doi: 10.1002/ar.24109
pmc: PMC6733676
mid: NIHMS1017452
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Nerve Tissue Proteins
0
Npas2 protein, mouse
0
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1630-1641Subventions
Organisme : NCRR NIH HHS
ID : C06 RR014529
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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